Substituted bicyclic compounds useful as T cell activators

Abstract

Disclosed are compounds of Formula (I): or a salt thereof, wherein: X is CR 6 or N; Y is CR 3 or N; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and m are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGKα) and diacylglycerol kinase zeta (DGKζ), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

What is claimed is: 
     
       1. A compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein: 
         X is or N; 
         Y is CR 3  or N; 
         L is —O—, —S—, —S(O) 2 —, —NR 4c —, or —NR 4d C(O)—; 
         R 1  is H, F, Cl, Br, —CN, C 1-3  alkyl substituted with zero to 4 R 1a , C 3-4  cycloalkyl substituted with zero to 4 R 1a , C 1-3  alkoxy substituted with zero to 4 R 1a , —C(O)NR a R a , —NR a R a , —S(O) n R e , or —P(O)R e R e ; 
         each R 1a  is independently F, Cl, —CN, —OH, —OCH 3 , or —NR a R a ; 
         each R a  is independently H or C 1-3  alkyl; 
         each R e  is independently C 3-4  cycloalkyl or C 1-3  alkyl substituted with zero to 4 R 1a ; 
         R 2  is H, C 1-3  alkyl substituted with zero to 4 R 2a , C 2-3  alkenyl substituted with zero to 4 R 2a , or C 3-4  cycloalkyl substituted with zero to 4 R 2a ; 
         each R 2a  is independently F, Cl, —CN, —OH, —O(C 1-2  alkyl), C 3-4  cycloalkyl, C 3-4  alkenyl, or C 3-4  alkynyl; 
         R 3  is H, F, Cl, Br, —CN, C 1-3  alkyl, C 1-2  fluoroalkyl, C 3-4  cycloalkyl, C 3-4  fluorocycloalkyl, —NO 2 , or pyridinyl substituted with zero to 2 R 3a ; 
         each R 3a  is halo, —CN, C 1-3  alkyl, or C 1-3  alkoxy; 
         R 4  is R 4a , —CH 2 R 4a , or —CH 2 CH 2 R 4a ; 
         R 4a  is C 3-6  cycloalkyl, C 5-14  heterocyclyl, C 6-10  aryl, or C 5-14  heteroaryl, each substituted with zero to 4 R 4b ; 
         each R 4b  is independently F, Cl, Br, —CN, —OH, C 1-6  alkyl, C 1-3  fluoroalkyl, C 1-4  hydroxyalkyl, —(CH 2 ) 1-2 O(C 1-3  alkyl), C 1-4  alkoxy, —O(C 1-4  hydroxyalkyl), C 1-3  fluoroalkoxy, —OCH 2 CH═CH 2 , —OCH 2 C≡CH, —C(O)(C 1-4  alkyl), —C(O)OH, —C(O)O(C 1-4  alkyl), —C(O)NH 2 , —C(O)NH(C 1-4  alkyl), —C(O)N(C 1-4  alkyl) 2 , —NR c R c , —NR a S(O) 2 (C 1-3  alkyl), —NR a C(O)(C 1-3  alkyl), —NR a C(O)O(C 1-4  alkyl), —P(O)(C 1-3  alkyl) 2 , —S(O) 2 (C 1-3  alkyl), —O(CH 2 ) 1-2 (C 3-6  cycloalkyl), —O(CH 2 ) 1-2 (morpholinyl), C 3-6  cycloalkyl, cyanocyclopropyl, methylazetidinyl, acetylazetidinyl, triazolyl, tetrahydropyranyl, morpholinyl, thiophenyl, methylpiperidinyl, or —CR c R c (phenyl); 
         each R c  is independently H or C 1-2  alkyl; 
         R 4c  is H, C 1-6  alkyl, or R 4a ; 
         R 4d  is H or C 1-6  alkyl; 
         each R 5  is independently F, Cl, —CN, —OH, C 1-6  alkyl substituted with zero to 4 R g , C 1-3  alkoxy substituted with zero to 4 R g , C 2-4  alkenyl substituted with zero to 4 R g , C 2-4  alkynyl substituted with zero to 4 R g , —(CH 2 ) 1-2 (C 3-4  cycloalkyl substituted with zero to 4 R g ), phenyl substituted with zero to 4 R g , oxadiazolyl substituted with zero to 3 R g , pyridinyl substituted with zero to 4 R g , —(CH 2 ) 1-2 (heterocyclyl substituted with zero to 4 R g ), —(CH 2 ) 1-2 NR c C(O)(C 1-4  alkyl), —(CH 2 ) 1-2 NR c C(O)O(C 1-4  alkyl), —O(CH 2 ) 1-2 (heterocyclyl substituted with zero to 4 R g ), —(CH 2 ) 1-2 NR c S(O) 2 (C 1-4  alkyl), —C(O)(C 1-4  alkyl), —C(O)OH, —C(O)O(C 1-4  alkyl), —C(O)O(C 3-4  cycloalkyl), —C(O)NR a R a , or —C(O)NR a (C 3-4  cycloalkyl), or two R 5  attached to the same carbon atom form ═O; 
         each R g  is independently F, Cl, —CN, —OH, C 1-3  alkoxy, C 1-3  fluoroalkoxy, —O(CH 2 ) 1-2 O(C 1-2  alkyl), C 3-5  cycloalkyl, or —NR c R c ; 
         each R 6  is H, F, Cl, —CN, —CH 3 , —CH 2 F, —CHF 2 , —CF 3 , or —OCH 3 ; 
         R 7  is H or —CH 3 ; 
         m is zero, 1, 2, or 3; and 
         n is zero, 1, or 2. 
       
     
     
       2. The compound according to  claim 1  or a salt thereof, wherein:
 R 1  is H, F, Cl, Br, —CN, C 1-3  alkyl substituted with zero to 4 R 1a , cyclopropyl substituted with zero to 3 R 1a , C 1-3  alkoxy substituted with zero to 3 R 1a , —C(O)NR a R a , —NR a R a , —S(O) n CH 3 , or —P(O)(CH 3 ) 2 ; 
 each R 1a  is independently F, Cl, or —CN; 
 each R a  is independently H or C 1-3  alkyl; 
 R 2  is H, C 1-2  alkyl substituted with zero to 2 R 2a , or C 2-3  alkenyl substituted with zero to 2 R 2a ; 
 each R 2a  is independently F, Cl, —CN, —OH, —O(C 1-2  alkyl), cyclopropyl, C 3-4  alkenyl, or C 3-4  alkynyl; 
 R 3  is H, F, Cl, Br, —CN, C 1-2  alkyl, C 1-2  fluoroalkyl, C 3-4  cycloalkyl, —NO 2 , or pyridinyl substituted with zero to 1 R 3a ; 
 R 4a  is C 3-6  cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, phenyl, naphthalenyl, furanyl, pyranyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, triazolyl, indolyl, indazolyl, phthalazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, benzooxazolyl, benzothiazolyl, benzoimidazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, naphthyridinyl, or dihydrobenzo[b][1,4]dioxepinyl, each substituted with zero to 3 R 4b ; 
 each R 4b  is independently F, Cl, Br, —CN, —OH, C 1-6  alkyl, C 1-2  fluoroalkyl, C 1-3  hydroxyalkyl, —(CH 2 ) 1-2 O(C 1-3  alkyl), C 1-4  alkoxy, —O(C 1-3  hydroxyalkyl), C 1-2  fluoroalkoxy, —C(O)(C 1-3  alkyl), —C(O)OH, —C(O)O(C 1-3  alkyl), —C(O)NH 2 , —C(O)NH(C 1-3  alkyl), —C(O)N(C 1-3  alkyl) 2 , —NR c R c , —S(O) 2 (C 1-2  alkyl), C 3-6  cycloalkyl, or —CR c R c (phenyl); 
 R 4c  is H, C 1-4  alkyl, or R 4a ; 
 R 4d  is H or C 1-4  alkyl; 
 each R 5  is independently F, —CN, —OH, C 1-5  alkyl substituted with zero to 4 R g , C 1-3  alkoxy substituted with zero to 3 R g , C 2-3  alkenyl substituted with zero to 4 R g , C 2-3  alkynyl substituted with zero to 4 R g , —(CH 2 ) 1-2 (C 3-4  cycloalkyl substituted with zero to 4 R g ), phenyl substituted with zero to 3 R g , oxadiazolyl substituted with zero to 3 R g , pyridinyl substituted with zero to 3 R g , —(CH 2 ) 1-2  (heterocyclyl substituted with zero to 4 R g ), —O(CH 2 ) 1-2 (heterocyclyl substituted with zero to 4 R g ), —(CH 2 ) 1-2 NR c C(O)(C 1-4  alkyl), —(CH 2 ) 1-2 NR c C(O)O(C 1-4  alkyl), —(CH 2 ) 1-2 NR c S(O) 2 (C 1-4  alkyl), —C(O)(C 1-4  alkyl), —C(O)OH, —C(O)O(C 1-4  alkyl), —C(O)O(C 3-4  cycloalkyl), —C(O)NR a R a , or —C(O)NR a (C 3-4  cycloalkyl); and 
 each R 6  is H, F, or —CH 3 . 
 
     
     
       3. The compound according to  claim 1  or a salt thereof, wherein:
 L is —O—, —NH—, —N(CH 3 )—, or —N(CH 3 )C(O)—; 
 R 1  is F, Cl, Br, —CN, —OCH 3 , or —C(O)NH 2 ; 
 R 2  is —CH 3 ; 
 R 3  is H, F, Cl, Br, —CN, —CH 3 , —NO 2 , methylpyridinyl, or methoxypyridinyl; 
 R 4  is R 4a  or —CH 2 R 4a ; 
 R 4a  is cyclohexyl, phenyl, indazolyl, phthalazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, benzooxazolyl, benzothiazolyl, quinolinyl, quinoxalinyl, quinazolinyl, 1,7-naphthyridinyl, or dihydrobenzo[b][1,4]dioxepinyl, each substituted with zero to 3 R 4b ; 
 each R 4b  is independently F, Cl, Br, —CN, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , —C(CH 3 ) 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —C(CH 3 ) 2 CH 2 CH 3 , —CHF 2 , —CF 3 , —OCH 3 , —OCH(CH 3 ) 2 , —OC(CH 3 ) 3 , —OCF 3 , —C(O)N(CH 3 ) 2 , —S(O) 2 CH 3 , —CH 2 (phenyl), —C(CH 3 ) 2 (phenyl), cyclopropyl, cyclopentyl, or cyclohexyl; 
 each R 5  is independently hydrogen, F, —OH, C 1-2  alkyl, C 1-3  alkoxy, —CH 2 CF 3 , —OCH 2 CH 2 OCH 3 , —OCH 2 CH 2 N(CH 3 ) 2 , —OCH 2 (cyclopropyl), or —OCH 2 CH 2 (morpholinyl); and 
 each R 6  is H. 
 
     
     
       4. The compound according to  claim 1  or a salt thereof, wherein:
 Y is CR 3 . 
 
     
     
       5. The compound according to  claim 1  or a salt thereof, wherein:
 Y is N. 
 
     
     
       6. The compound according to  claim 1  or a salt thereof, wherein L is —O—. 
     
     
       7. The compound according to  claim 1  or a salt thereof, wherein L is —NR 4c —. 
     
     
       8. The compound according to  claim 1  or a salt thereof, wherein L is —NR 4d C(O)—. 
     
     
       9. The compound according to  claim 1  or a salt thereof, having a structure selected from: 
       
         
           
           
               
               
           
         
       
     
     
       10. A compound or a salt thereof, wherein said compound is:
 6-chloro-4-(4-(3-methoxyphenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-2-oxo-4-(4-(2-(trifluoromethyl)phenoxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(3,4-difluorophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-2-oxo-4-(4-(3-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(4-methoxyphenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 4-(4-(4-(tert-butyl)phenoxy)piperidin-1-yl)-6-chloro-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(4-chlorophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(3-fluoro-4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(2-chlorophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-2-oxo-4-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(4-fluorophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-2-oxo-4-(4-(p-tolyloxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-2-oxo-4-(4-(m-tolyloxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(2-chloro-5-fluorophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-2-oxo-4-(4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 4-((1-(6-chloro-3-cyano-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridin-4-yl)piperidin-4-yl)oxy)-N,N-dimethylbenzamide; 
 4-(4-(4-bromo-2-methylphenoxy)piperidin-1-yl)-6-chloro-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(3-chlorophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(3-chloro-5-fluorophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-4-(4-(2-methyl-4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-2-oxo-4-(4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 4-(4-(4-(tert-butoxy)phenoxy)piperidin-1-yl)-6-chloro-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(4-cyanophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-2-oxo-4-(4-(2-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(3-cyanophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(2-methoxyphenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(4-fluoro-2-methoxyphenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(4-isopropylphenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(3-chloro-4-cyanophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(4-chloro-3-methoxyphenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(3-chloro-4-methylphenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(2-chloro-4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(3-chloro-4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(2-cyanophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(2-fluorophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-4-(4-(3-fluorophenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-chloro-1-methyl-2-oxo-4-(4-phenoxypiperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-bromo-1-methyl-2-oxo-4-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 6-methoxy-1-methyl-2-oxo-4-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 1-methyl-2,6-dioxo-4-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1,2,5,6-tetrahydro-1,5-naphthyridine-3-carbonitrile; 
 5-methyl-6-oxo-8-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2,7-dicarbonitrile; 
 5-methyl-7-nitro-6-oxo-8-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 4-(4-(4-(tert-butyl)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydroquinoline-6-carbonitrile; 
 5-methyl-6-oxo-8-(4-(4-(tert-pentyl)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-(4-benzylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-(4-butylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-(4-(4-propylphenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-(4-cyclopentylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-(4-cyclopropylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-(4-isopropyl-3-methylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-(4-((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-(4-(4-pentylphenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-(4-cyclohexylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-(4-(2-cyclohexylpropan-2-yl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-(4-(tert-butoxy)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((5-isopropoxypyridin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((5-chloropyridin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((6-(tert-butyl)pyridazin-3-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-(4-(quinoxalin-2-yloxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((2,6-dimethylpyrimidin-4-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-(4-(quinazolin-4-yloxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-(4-((2-methylpyrimidin-4-yl)oxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((7-chloro-4-methoxyquinolin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((1,7-naphthyridin-8-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-(4-(phthalazin-1-yloxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-(4-((2-(trifluoromethyl)pyrimidin-4-yl)oxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-(4-((5-(trifluoromethyl)pyridin-2-yl)oxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-(2-isopropyl-6-methylpyrimidin-4-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (+/−) 6-cyano-1-methyl-4-((3R,4R)-3-methyl-4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1,5-naphthyridin-2(1H)-one; 
 6-cyano-1-methyl-4-((3R,4R)-3-methyl-4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1,5-naphthyridin-2(1H)-one; 
 6-cyano-1-methyl-4-((3R,4R)-3-methyl-4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-1,5-naphthyridin-2(1H)-one; 
 5-methyl-8-((3R,4R)-3-methyl-4-(4-(tert-pentyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-(tert-butoxy)phenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-(tert-butyl)phenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(3-cyclopropylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-isopropylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4R)-3-methyl-4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-cyclopentylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(3,4-difluorophenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-cyclohexylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4R)-3-methyl-4-(m-tolyloxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-ethylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-cyclopropylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(2-fluoro-4-(trifluoromethyl)phenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(2,4-difluorophenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-fluoro-2-(trifluoromethyl)phenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4R)-3-methyl-4-(p-tolyloxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(3-isopropylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(3-(tert-butyl)phenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(2-fluoro-6-(trifluoromethyl)phenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(2,6-difluorophenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-fluorophenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4R)-3-methyl-4-(2,4,6-trifluorophenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-6-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4R)-3-methyl-4-(m-tolyloxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2,7-dicarbonitrile; 
 8-((3R,4R)-3-ethyl-4-(3-isopropylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-ethyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-ethyl-4-(4-isopropylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-ethyl-4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-ethyl-4-(4-(tert-pentyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-(tert-butyl)phenoxy)-3-ethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(3-cyclopropylphenoxy)-3-ethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(4-(tert-butoxy)phenoxy)-3-ethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-ethyl-4-(4-isopropoxyphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-ethyl-4-(3-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-3-ethyl-4-(3-isopropylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-(3-(tert-butyl)phenoxy)-3-ethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4S)-3-methyl-4-(4-(tert-pentyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-(4-(tert-butoxy)phenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-(4-(tert-butyl)phenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-(4-isopropylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-(3-cyclopropylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-(4-isopropylphenoxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (+/−) 5-methyl-8-((3R,4S)-3-methyl-4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carboxamide; 
 (+/−) 5-methyl-8-((3R,4S)-3-methyl-4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4S)-3-methyl-4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4S)-3-methyl-4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4S)-3-methyl-4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2,7-dicarbonitrile; 
 8-((3R,4R)-3-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-ethyl-4-(4-fluoro-3-propylphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-(3-(tert-butyl)phenoxy)-3-ethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-4-((5-isopropoxypyridin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-3-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-((5-isopropylpyridin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-((5-(difluoromethyl)pyridin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-(4-isopropylpyridin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-(6-isopropylpyridin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4S)-3-methyl-4-(pyrimidin-2-yloxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-((4-methoxypyrimidin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4S)-3-methyl-4-((5-propylpyrimidin-2-yl)oxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4S)-3-methyl-4-((2-methylpyrimidin-4-yl)oxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-((5-ethylpyrimidin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4S)-3-methyl-4-((5-(trifluoromethyl)pyrimidin-2-yl)oxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-((5-cyclopropylpyrimidin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4S)-4-((5-cyclopropylpyridin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4S)-3-methyl-4-((5-(trifluoromethyl)pyridin-2-yl)oxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (+/−) 8-((3R,4S)-4-((5-isopropoxypyridin-2-yl)oxy)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (+/−) 5-methyl-8-((3R,4R)-3-methyl-4-(4-(tert-pentyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2,7-dicarbonitrile; 
 5-methyl-8-((3R,4R)-3-methyl-4-(4-(tert-pentyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2,7-dicarbonitrile; 
 5-methyl-8-((3R,4R)-3-methyl-4-(4-(tert-pentyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2,7-dicarbonitrile; 
 (+/−) 8-(4-((5-isopropoxypyridin-2-yl)oxy)-3,3-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((5-isopropoxypyridin-2-yl)oxy)-3,3-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((5-isopropoxypyridin-2-yl)oxy)-3,3-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (+/−) 5-methyl-8-((3R,4S)-3-methyl-4-((4-(trifluoromethoxy)benzyl)oxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (+/−) 5-methyl-8-((3R,4S)-3-methyl-4-((4-(trifluoromethoxy)benzyl)oxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carboxamide; 
 7-fluoro-5-methyl-6-oxo-8-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 7-chloro-5-methyl-6-oxo-8-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 7-bromo-5-methyl-6-oxo-8-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 7-(6-methoxypyridin-3-yl)-5-methyl-6-oxo-8-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 7-(2-methoxypyridin-4-yl)-5-methyl-6-oxo-8-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (+/−) 6-bromo-1-methyl-4-((3R,4R)-3-methyl-4-(4-(tert-pentyl)phenoxy)piperidin-1-yl)-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carbonitrile; 
 8-((2S,5S)-4-((5-isopropoxypyridin-2-yl)oxy)-2,5-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2R,5R)-4-((5-isopropoxypyridin-2-yl)oxy)-2,5-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 4-((2R,5S)-4-((5-isopropoxypyridin-2-yl)oxy)-2,5-dimethylpiperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 4-((2S,5R)-4-((5-isopropoxypyridin-2-yl)oxy)-2,5-dimethylpiperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 4-((2R,5S)-2,5-dimethyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 4-((2S,5R)-2,5-dimethyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 4-((2R,5R)-2,5-dimethyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 8-((2S,5S)-2,5-dimethyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (±)-trans-8-(3-hydroxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (±)-trans-8-(3-methoxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-ethoxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (±)-cis-8-(3-fluoro-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (±)-trans-8-(3-hydroxy-4-((5-isopropoxypyridin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (±)-trans-8-(4-((5-isopropoxypyridin-2-yl)oxy)-3-methoxypiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (±)-trans-6-chloro-4-(3-hydroxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1-methylpyrido[3,2-d]pyrimidin-2(1H)-one; 
 (±)-trans-4-(3-hydroxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 6-chloro-4-((3R,4R)-3-methoxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1-methylpyrido[3,2-d]pyrimidin-2(1H)-one; 
 (±)-trans-4-(3-hydroxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 4-((3R,4R)-3-ethoxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 8-((2S,5R)-4-((5-methoxypyridin-2-yl)amino)-2,5-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 N-((2S,5R)-1-(6-cyano-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridin-4-yl)-2,5-dimethylpiperidin-4-yl)-4-fluoro-N-methylbenzamide; 
 N-(1-(6-cyano-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridin-4-yl)-3-methylpiperidin-4-yl)-4-fluoro-N-methylbenzamide; 
 N-(1-(3,6-dicyano-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridin-4-yl)-3-methylpiperidin-4-yl)-N-methyl-4-(trifluoromethyl)benzamide; 
 8-((2S,4S,5S)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2R,4S,5S)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,4R,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2R,4R,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2R,4S,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,4S,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 6-chloro-4-((2S,4R,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-1-methylpyrido[3,2-d]pyrimidin-2(1H)-one; 
 4-((2S,4R,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 6-chloro-4-((2R,4R,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-1-methylpyrido[3,2-d]pyrimidin-2(1H)-one; 
 4-((2R,4R,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 6-chloro-4-((2R,4S,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-1-methylpyrido[3,2-d]pyrimidin-2(1H)-one; 
 4-((2R,4S,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 6-chloro-4-((2S,4S,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-1-methylpyrido[3,2-d]pyrimidin-2(1H)-one; 
 4-((2S,4S,5R)-5-ethyl-4-((5-isopropoxypyridin-2-yl)oxy)-2-methylpiperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 8-((2S,4S,5R)-5-ethyl-2-methyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2R,4S,5R)-5-ethyl-2-methyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2R,4R,5R)-5-ethyl-2-methyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2R,4S,5R)-2,5-dimethyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,4R,5S)-2,5-dimethyl-4-(p-tolyloxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,4R,5S)-4-(3-chlorophenoxy)-2,5-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,4R,5S)-4-(3-cyanophenoxy)-2,5-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,4R,5S)-4-(4-fluorophenoxy)-2,5-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,5S)-2,5-dimethyl-4-((4-(trifluoromethyl)phenyl)amino)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile (316A); 
 8-(2,5)-dimethyl-4-(methyl(4-(trifluoromethyl)phenyl)amino)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,5S)-2,5-dimethyl-4-(methyl(3-(trifluoromethyl)phenyl)amino)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((4-fluorobenzyl)(methyl)amino)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2,7-dicarbonitrile; 
 8-(4-((4-fluorobenzyl)(methyl)amino)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-(4-((4,4-difluorocyclohexyl)(methyl)amino)-3-methylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2,7-dicarbonitrile; 
 8-((2S,5R)-4-((4-fluorobenzyl)(methyl)amino)-2,5-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,5S)-4-((4-fluorobenzyl)(methyl)amino)-2,5-dimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((2S,5S)-4-((5-Isopropoxypyridin-2-yl)oxy)-2,4,5-trimethylpiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-((2S,5S)-2,4,5-trimethyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 1-methyl-2-oxo-4-((2S,5S)-2,4,5-trimethyl-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 trans-8-(3-ethoxy-4-phenoxypiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-(2-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-(4-isopropoxyphenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-(3-(trifluoromethoxy)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-(4-(methylsulfonyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-((2-methylbenzo[d]oxazol-5-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-4-(4-chloro-3-fluorophenoxy)-3-ethoxypiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-((2-(trifluoromethyl)pyridin-4-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 trans-8-(3-ethoxy-4-((6-(trifluoromethyl)pyridin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-((4-(trifluoromethyl)pyridin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 trans-8-(3-ethoxy-4-((5-(trifluoromethyl)pyridin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 cis-8-(3-ethoxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 cis-8-(3-ethoxy-4-((5-isopropoxypyridin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 trans-8-4-(benzo[d]thiazol-2-yloxy)-3-ethoxypiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-((6-isopropoxypyridazin-3-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-((5-isopropoxypyrazin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-((5-isopropoxypyrimidin-2-yl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-((3-(trifluoromethyl)benzyl)oxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3S,4S)-3-ethoxy-4-((5-isopropoxypyridin-2-yl)methoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-(2-(dimethylamino)ethoxy)-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-(cyclopropylmethoxy)-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 8-((3R,4R)-3-(2-methoxyethoxy)-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-8-((3R,4R)-3-(2-morpholinoethoxy)-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 5-methyl-6-oxo-8-((3R,4R)-3-(2,2,2-trifluoroethoxy)-4-(3-(trifluoromethyl)phenoxy) piperidin-1-yl)-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 trans-8-(3-isopropoxy-4-(3-(trifluoromethyl)phenoxy)piperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 trans-8-(4-((5-isopropoxypyridin-2-yl)oxy)-3-ethoxypiperidin-1-yl)-5-methyl-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile; 
 (±)-trans-6-chloro-4-(3-ethoxy-4-((5-isopropoxypyridin-2-yl)oxy)piperidin-1-yl)-1-methylpyrido[3,2-d]pyrimidin-2(1H)-one; 
 trans-4-(3-ethoxy-4-((5-isopropoxypyridin-2-yl)oxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile; 
 trans-4-(3-ethoxy-4-phenoxypiperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d] pyrimidine-6-carbonitrile; or 
 4-((3S,4S)-3-ethoxy-4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyrimidine-6-carbonitrile. 
 
     
     
       11. A pharmaceutical composition comprising a compound according to  claim 1  or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier.